Pharmaceutical compositions that contain pharmaceutically active compounds, such as drugs and vitamins, or other pharmaceutical compositions, such as fluids to be delivered to a patient intravenously, must be sterilized to prevent the patient who is receiving such a pharmaceutical composition from becoming infected with microorganisms, such as bacteria, and to prevent spoilage of the pharmaceutical composition.
One common method of sterilizing a pharmaceutical composition is by heating the composition to kill any microorganisms. However, many pharmaceutically active compounds are destroyed or degraded when exposed to heat. In general, the higher the temperature, the more the composition degrades. Similarly, the longer the composition is exposed to heat, the more the composition degrades. A method that has been used to sterilize compositions that are relatively insensitive to heat degradation is to place those compositions in an autoclave, which heats the compositions. In addition to not being suitable for compositions that are heat sensitive, autoclaving is usually carried out terminally; that is, after the bulk composition has been prepared, filled and sealed in the final container, which can be inefficient and time consuming. Also, the elevated temperatures associated with autoclaving promote undesirable chemical reactions between the pharmaceutical composition and the container or its component parts.
Because many pharmaceutical compositions are heat sensitive, autoclaving such compositions is not possible. Instead, a heat sensitive composition, if in the form of a solution, may be filtered so that any harmful microorganisms are removed from the solution. However, filtering can be a costly process and cannot be used to sterilize pharmaceutical compositions that are not true solutions, such as mixtures and suspensions. Moreover, sterilization by filtration is very difficult if the solution has a high viscosity.
Another sterilization process that does not employ heat is radiation sterilization. In this process of sterilization, a composition to be sterilized is irradiated with certain types of radiation, which can include high-energy particles as well as portions of the electromagnetic spectrum. Again, however, many pharmaceutical compositions cannot be sterilized by radiation because irradiation of such pharmaceutical compositions destroys or degrades the compositions or the containers in which the compositions are stored.
Chemicals have also been used to sterilize compositions. Such chemicals are typically antibacterial substances. However, the addition of such chemicals to a pharmaceutical composition may not be desired, as the chemicals may be detrimental to the patient to whom the pharmaceutical composition is to be administered or may be detrimental to any of the various components of a pharmaceutical composition. Moreover, such chemicals, at low concentrations, can be bacteriostatic rather than bactericidal; that is, they prevent the growth of bacteria, but may not kill them.
A sterilization method for sterilizing pharmaceutical compositions using heat that does not result in unacceptable degradation of the pharmaceutical composition is provided by the present invention.
The invention is a method of controlling the degree of degradation of a heat sensitive pharmaceutical composition by quantification and control of the thermal input required to sterilize the composition.